Poliovirus Surveillance And Emergency Response For Cases Caused By Vaccine-derived Polioviruses At The Endgame Of Polio-free In Shandong Province Of China

【Background】In 1988,the World Health Organization(WHO) launched a global initiative to eradicate polio.In the following 20 years,countries in the world were all applying themselves to the Global Polio Eradication Initiative and made a great progress.At present,there are 3 regions of all 6 WHO regions had achieved the goal of polio-free,such as the WHO European Region,Western Pacific Region(WPR) and the Region of the Americas.In October 2000,china entered the maintaining period of polio-free in Global Polio Eradication initiative.In the polio-free region,re-infected wild poliovirus could be spread again and caused polio outbreaks because of low rates of coverage with oral poliovirus vaccine(OPV).Vaccine-Derived Poliovirus(VDPV) which produced by OPV vaccine virus variation forms into circulating of Vaccine-Derived Poliovirus(cVDPVs),thus caused epidemic in the low immunization coverage areas of OPV.The situation above mentioned presents the new challenge for the maintaining of polio-free and the Global Polio Eradication Initiative.There are four primary strategies in the period of maintaining polio-free,include improving and maintaining high level routine immunization coverage of OPV,OPV supplementary immunization activities(SIAs),high quality of Acute Flaccid Paralysis(AFP) surveillance system and the consummation Expanded Programme on Immunization management system. Once cVDPVs appears,outbreaks or epidemic may happen,which belong to magnitude emergency public health events.The events of VDPV cases had happened for some times in our countries,although some measures had been taken in different province,but how to explore VDPV occuring and circulation correlation factor furtherly,and how to build and perfect the pertinence emergency treatment strategy has the important theory and the practical significance to our country and the whole world.【Objective】To analyze the virology surveillance for acute flaccid paralysis(AFP) cases on the endgame of poliomyelitis free from 2000 to 2006 in Shandong province.To evaluate synthetically the sensitivity,timeliness,accuracy and integrity of the AFP surveillance system in Shandong province.To monitor the vaccine-variant polioviruses,then we have done a molecule epidemiology study to vaccine mutant of poliovirus to explore it's rules and characters.In 2007,a case of VDPV was discovered in Shandong province for the first time.And we should do more study to the VDPV event,include analyzing completely and evaluating the emergency measures and effects.That provide scientific basis to establish and perfect project of emergency response for VDPV.Part 1 Poliovirus Surveillance at the Endgame of Polio-free in Shandong Province of China【Methods】Virus isolation serotype identification and neutralization test were according to the WHO.Polio Laboratory Manual,and all polio-positive strains were sent to National Poliomylitis Laboratory for type determination with ELISA and PCR-RFLP.VP1 genomic sequencing technique was used to analyze the molecular character of vaccine-variant polioviruses,the result were analyzed with Sequencher, DNAStar.【Results】The surveillance indicator of AFP system all reached and exceeded the demand of WHO and Ministry of Health from 2000 to 2007 in Shandong province. 270 strains of PV were isolated from 3259 AFP case in 2000～2007,and the type of PVⅡis predominant strain.At the same time,the isolation rate of NPEV was also highly kept.The whole year PV occurred,but there is no obvious distribution rule, and there is no obvious region cluster,but there is obvious difference among different ages,the incidence rate is the highest in children aged under 5,PV cases is 226 (83.70%).Among AFP cases,residue paralysis proportion in children of the zero-dose vaccination is higher than the full dose vaccination,and the difference between two groups mentioned above is significant(χ~2=23.18,P=0.000),29 virus strains was studied by molecule epidemiology,The type of PVⅡis the chief type from 2000 to 2004,PVⅢis chief type from 2005 to 2006,PVⅡis chief type in 2007 again.One of neurovirulence determinant sites of 5 PVⅠand 13 PVⅡwas validated.Two concentrated variable sites in 54 and 293 amino acid sequences were found in VP1 section among 11Ⅲstrains.Phylogenetic analysis shows that the homology of all the strains approximated to SabinⅢtype.【Conclusions】The surveillance system of AFP and virology in Shandong province has higher sensitivity,timeliness,integrality and accuracy,and we have grasped the poliovirus integrated features and Molecular Biological Traits of vaccine variation strains.【Recommendations】When increasing the rate of vaccination,we should further enhance virology monitoring the AFP cases,pay close attention to vaccine strains of polio virus variation,early detect the importation of wild polio virus strains and vaccine variation strain,take prompt emergency measures to block the spread of the virus,continue to maintain the status of polio free until the global eradication of polio to achieve the goal. Part 2 Emergency Response for the First Event of Vaccine-derived Polioviruses at the Endgame of Polio-free in Shandong Province of China【Methods】Shandong province conducted field epidemiological investigation,rapid investigation of immunization coverage,actively searched for AFP cases, management of cases,virology surveillance in laboratory,and Supplementary Immunization Activities(SIA) to detect and control the VDPV event.【Results】On April 2007,a VDPV incident had happened in Shandong province,and a series of measures had been taken to control this epidemic situation.The epidemiology survey showed that two cases had taken 1 and 11 times vaccine respectively and there is no missing report in both cities,and no direct and indirect relationship between two cases,the third and sixth specimen of 31 subsequent specimens from case 2 were positive after emergency immunity,and didn't reach the standard of VDPV,and 15 subsequent specimens from case 1 was negative.Immune deficiency didn't been detected in serum of VDPV case.4 virus strains had been isolated and identified from 188 stools of close contacting person,but didn't reach the VDPV standard.60 stools which gathered from the same group after emergency immunity were negative.The result of Neutralizing Antibodies in serum collected from children above mention showed that the level poliovirus antibody level was high in both counties,and the vaccination rate was high too.For the first time,188 children were investigated and the vaccination rate is 96.81%,and the second time,229 were investigated and the rate is 100%.【Conclusions】The two cases of VDPV,which happened in 2007,is mutually independent,and didn't advance to cVDPVs.And we have taken a series of emergency measures to control the VDPV incidents,we have a clear case definition, confirm the attribute of VDPV,interrupted the transmission of VDPV,made good result,and accumulated experience for dealing with these emergency standard of our country. 【Recommendations】Establish and improve emergency response project for magnitude emergency VDPV events.